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EP-4514413-B1 - METHOD FOR THE PRODUCTION OF BIOLOGICAL TISSUE

EP4514413B1EP 4514413 B1EP4514413 B1EP 4514413B1EP-4514413-B1

Inventors

  • RZANY, ALEXANDER
  • HARDER, CLAUS
  • LITSCHKO, ROBERT
  • MUELLER, HEINZ

Dates

Publication Date
20260506
Application Date
20230414

Claims (15)

  1. Method for the preparation of a biodegradable tissue, wherein the method comprises or consists of the following steps: a) providing one or more native biological tissue(s) or one or more decellularized biological tissue(s), b) structurally stabilizing the one or more native biological tissue(s) or the one or more decellularized biological tissue(s) with a tissue water replacing material to obtain a structurally stabilized tissue, c) providing at least one, preferably two, permeable material layer(s), d) placing the structurally stabilized tissue on, in or between the permeable material layer(s); e) providing one or more pressure compensation layers and covering the structurally stabilized tissue or the at least one, preferably two, permeable material layer(s), with the one or more pressure compensation layers; f) drying the structurally stabilized tissue while applying a pressure to the structurally stabilized tissue to obtain a dried tissue, g) optionally removing the dried tissue from the permeable material layer(s) and the optional pressure compensation layer(s);
  2. The method according to claim 1, wherein the native biological tissue is a collagen containing biological tissue or the decellularized biological tissue is based on a collagen containing biological tissue.
  3. The method according to claim 1, wherein the native biological tissue is dura mater or the decellularized biological tissue is based on dura mater.
  4. The method according to any one of the preceding claims, wherein the at least one, preferably two, permeable material layer(s) comprise or consist of a polymer.
  5. The method according to any one of the preceding claims, wherein the at least one, preferably two, permeable material layer(s) has/have a pore size in the range of 10 to 60 µm.
  6. The method according to any one of the preceding claims, wherein the pressure compensation layer has a compression hardness in the range of 20 kPa to 80 kPa, preferably 30 kPa to 70 kPa, more preferably 40 kPa to 60 kPa, even more preferably 60 kPa.
  7. Biodegradable tissue obtained by the method according to one of the preceding claims.
  8. Biodegradable tissue according to claim 7 which is a biodegradable dura mater obtained by the method according to one of the claims 3 to 6, being optically transparent and/ or having a thickness of less than 80 µm, preferably between 60 and 20 µm.
  9. Medical implant comprising the biodegradable tissue according to claims 7 or 8 or obtained by the method according to any one of the claims 1 to 6.
  10. The medical implant according to claim 9, wherein the medical implant is selected from a covered stent or a stent graft.
  11. The medical implant according to claim 9, wherein the medical implant is a cardiovascular implant, an endovascular prostheses, an endoprostheses, an esophageal implant, a bile duct implant, a dental implant, an orthopedic implant, a neurological implant, a microchip containing implant, a covered stent, a stent graft, a bone implant, a glucose sensor implant, a neurostimulator, a cochlear implant, an endoprostheses for closing persistent foramen ovale, an endoprostheses for closing an atrial septal defect, a left atrial appendage closure device, a pacemaker, a leadless pacemaker, a defibrillator, a prosthetic heart valve, a venous valve, a tooth implant.
  12. Biodegradable biological tissue obtained by a method according to one of the claims 1 to 6 for use as a medical implant or for use in a medical implant.
  13. Biodegradable biological tissue obtained by a method according to one of the claims 1 to 6 for use as a tissue patch.
  14. Biodegradable dura mater obtained by a method according to one of the claims 3 to 6 for use as a tissue patch or for use as a tubular medical implant or for use of repairing dura mater defects.
  15. Device for the preparation of biodegradable tissue according to a method of any one of claims 1 to 6 comprising: - at least one pressure applying unit, - one or more pressure compensation layer(s) being arranged in the pressure applying unit and - one or more permeable material layer(s) being arranged in the pressure applying unit.

Description

The present invention is directed to a method for the preparation of a biodegradable tissue, the biogradable tissue obtained by said method, a medical implant comprising said biodegradable tissue and a device for preparation of the biodegradable tissue. A first aspect of the invention relates to a method for producing biodegradable and transparent biological tissue, preferably a collagen containing tissue. The (decellularized) biological tissue is first stabilized by a tissue water replacing material and then dried while applying an elevated pressure to the biological tissue. Also disclosed is a pressing unit/mold for stabilized drying of biological tissue (e.g. pericardium) under external pressure: The natively dried biological tissue is placed between two layers of a (technical) polyester fabric, which serves as drainage for the stabilizers and water. An open-cell polyurethane foam provides additional drainage while distributing the mechanical load. The two rigid outer forms are adjusted to a defined mechanical pressure (adjustable by the distance between the screwed outer forms) by means of screws. The remaining water is removed from the fabric by drying in the press mold in, for example, a climatic chamber. A method for three-dimensional shaping by means of rigid molded bodies on both sides are known, for example, from US 8,136,218 B2. In the method described therein, the tissue is placed between two rigid shaped bodies and chemically crosslinked in this state. A method of manufacturing a prosthetic heart valve that includes processing dried biological material has been disclosed in US 8,105,375. According to the method disclosed therein, the biological tissue is fixed or crosslinked with an aldehyde-containing solution (e.g., glutaraldehyde or formaldehyde solution), and treated with at least one aqueous solution containing at least one biocompatible and non-volatile stabilizer prior to drying. Chemical crosslinking by means of glutaraldehyde leads to inter- and intramolecular crosslinking in the collagen. Due to this the tissue cannot undergo enzymatic degradation. The cross-linked tissue is a non-biodegradable tissue. However, in some medical application a biodegradable tissue is required. However, the exemplary method of the prior art named above are subject to disadvantages. Thickness reduction is mostly based on chemical crosslinking under pressure, and thus on the principle of displacement of water from the original tissue, and an associated densification of the fibers of the tissue. However, if the tissue is limited from both sides by means of a fixed counterform as, for example, in the case of the use of two rigid molded bodies, there is no sufficient exchange surface for the water, and a very high pressure is necessary to be able to reduce this in turn. The rigid molded bodies are also unable to compensate for the naturally always present inhomogeneity in the tissue thickness. In areas of higher tissue thickness, this also results in pressure peaks which cause partial fiber compaction and the associated stiffening of the tissue. In addition, the rigid mold bodies hinder the access of substances to the tissue. Another problem of the prior art processes is that non-transparent tissue is obtained. However, in some application optical transparent tissue is required, e.g. for recognizing bleedings during an operation. US 2010/011564 A1 discloses a mold assembly and a method for forming a prosthetic heart valve. EP 3 156 083 A1 discloses a method for thickness control and three-dimensional shaping of biological tissue during fixing. With regard to the above-mentioned disadvantages of the prior art, an object of the first aspect of the first invention is to provide a method for the production of a biodegradable i.e. (substantially) non-crosslinked and optical transparent (collagenous) biological tissue. The scope of protection is defined by the claims.The references to methods of treatment by therapy or surgery in the description are to be interpreted as references to implants of the present invention for use in those methods. A method for the preparation of a biodegradable biological tissue is described in claim 1. The biological (starting) tissue must be thoroughly cleaned and prepared prior to implantation. As far as possible, the tissue is modified in such a way that it is not recognized by the body as foreign tissue, has as little calcification as possible, and has as long a service life as possible. According to the first aspect of the invention, the substantially non-crosslinked starting tissue, such as native biological tissue is processed to remove unwanted tissue residues. Unless otherwise explicitly stated the (starting) tissue to be treated throughout the application is to be understood as biological tissue. Biological tissue preferably has an organizational level intermediate between cells and a complete organ. The biological (starting) tissue may be an autologous, xenogeneic or allogene